Electronic device for weight control

ABSTRACT

Orally administrable polymer-carrying units for expanding in a stomach of a mammal to fill a space in the stomach, the polymer-carrying units including: a carrier; a plurality of polymer molecules expandable in aqueous solutions, releasably coupled to the carrier; and means for selectively decoupling the polymer molecules from the carrier so that the polymer molecules and carrier are released in the stomach, are provided.

CROSS REFERENCE TO RELATED APPLICATION(S)

This application is a divisional of U.S. Ser. No. 11/718,514, whichentered the national stage on Nov. 6, 2007 on the basis of InternationalPCT application Ser. No. PCT/CA2005/001693 filed on Nov. 4, 2005, andwhich claimed benefit under 35 U.S.C. §1.19(e) of U.S. Ser. No.60/625,092 filed Nov. 5, 2004, and U.S. Ser. No. 60/666,517, filed Mar.22, 2005, the entire contents of which are incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates to the field of ingestible microelectronicdosage forms, and more specifically to ingestible,electronically-controlled and timed dosage forms comprising expandablepolymeric material useful for weight control and the treatment ofobesity.

BACKGROUND OF THE INVENTION

Weight control and treatments for obesity have been the subjects of alarge amount of suggested diets, treatments and procedures, including,in the most severe cases of morbid obesity, device implantations and/ordirect surgical interventions. Recent comprehensive statistics from theNational Institutes of Health (USA) indicates that more that 40% ofAmericans are obese, with more than 20% of these individuals beingmorbidly obese. In addition, it can be estimated that at least twice asmany people are seeking to control their body weight, and/or areadhering to diets or other weight-control mechanisms. This isparticularly significant since obesity has been implicated as a leadingcause of various clinical conditions, including cardiovascular diseasesand diabetes.

Six major streams of research and development related to new treatmentsfor obesity are currently available: (1) diet regiments, anddiet-related supplements and treatments; (2) pharmacological treatmentusing specifically developed medications; (3) gastric stimulation usingimplantable electronic devices; (4) invasive surgical procedures relatedto gastric reduction; (5) intragastric balloons for reducing gastricvolume and introducing a sensation of satiety and fullness; and (6) oraladministration of cellulose or polymeric-based substances, which expandin the stomach and preclude their expulsion through the pylorus with theprocess of natural gastric peristalsis, thus introducing sensation offullness and satiety. These expanded polymeric substances subsequentlydisintegrate chemically to allow for their expulsion from the body withnatural gastrointestinal peristalsis.

Currently, there are very large numbers of various diets, dietsupplements, diet regimens, and combinations thereof, and their numbersare growing dramatically. However, in many cases, these weight lossstrategies do not work, or their success is very limited. The success ofthese techniques often varies widely between individuals, and they areoften not sustainable.

Weight-loss related pharmacological treatment based on specificallydeveloped and clinically-tested drugs and/or health supplements has alsonot been very successful. Numerous such therapies have been associatedwith various side effects, some of which are quite serious andlife-threatening. Therefore, commercially-available andclinically-proven diets and/or anti-obesity drugs and health supplementshave yet to be developed.

Recently developed techniques for gastric stimulation (see for examplesU.S. Pat. Nos. 6,684,104, 6,615,084, 6,606,523, 6,600,953, 6,542,776,6,535,764, and 6,449,511), involving surgical implantation of miniaturemicroelectronic devices have been proposed as an avenue to tackle moresevere cases of obesity, and particularly morbid obesity. The devicescan administer electrical signals to the stomach and adversely affectnormal propulsive gastric peristalsis. However, the procedures used forthe positioning of the electrode as well as the implantation of thedevice remain invasive, and the long-term effect of the treatmentremains unknown both in terms of sustainability and safety.

Surgical procedures related to gastric volume reduction are invasivemeasures to address the problem of obesity. Mortality rates ofprocedures like gastric bypass or direct gastric volume reduction canreach 2%, have prolonged recovery periods, and can be quite expensive.

Intragastric balloons or devices positioned in the stomach eithersurgically or endoscopically to reduce the effective gastric volume havebeen found effective in introducing early satiety and sensation offullness, thus contributing to reduced food intake, which has beenreliably related to sustainable weight loss (see for example U.S. Pat.Nos. 4,739,758, 4,485,805, 4,899,747, 5,234,454, 5,993,473, and6,579,301). More recently, wireless control of volume-controllingdevices in the stomach has been suggested (see for example U.S. Pat.Nos. 6,461,293, 6,454,699, 6,453,907, 6,460,543, and 6,450,946).However, these techniques remain invasive and can be associated withserious and sometimes life-threatening side-effects.

Most recently, the use of swellable polymers has been proposed tofacilitate the reduction of gastric volume for treating obesity (see forexample U.S. Pat. Nos. 5,750,585, 6,271,278, German Pat. No.NDN-050003290517, and US Patent Application No. 20040192582). Compressedcellulose derivatives, or dehydrated hydrophilic polymers are introducedorally in the stomach, and expand to the point of not being able to passthrough the pylorus, thus effectively achieving non-invasively what anintragastric balloon or another gastric volume-reducing device wouldachieve. However, the subsequent decomposition and/or degradation ofthese polymers to allow for expulsion through natural peristalsis can bevery problematic. More specifically, the decomposition and/ordegradation rate is not precisely controlled, and the volume and thenumber of the decomposing/degrading parts or portions is unknown. Moreimportantly, since this decomposition is pharmacologically-based, itstiming cannot be precisely controlled since it would depend on numerousexternal factors related to the gastric pH, enzyme content, peristalticpattern, and the anatomy of the particular patient. Because of theuncontrolled nature of the decomposition, it is possible that the volumeof the stomach may remain in an expanded state for long intervals oftime, which can lead to serious side-effects and significant discomfort.Moreover, improper decomposition and/or degradation may lead to seriouscomplications such as small bowel obstructions.

Consequently, the need has arisen for non-invasive techniques orproducts that can be easily used for prolonged and controlled reductionof gastric volume for use in facilitating weight loss, which addresssome of the problems encountered in the prior art.

SUMMARY OF THE INVENTION

According to a broad aspect of this invention, there is provided anorally administrable polymer-carrying unit for expanding in a stomach ofa mammal to fill a space in the stomach, the polymer-carrying unitincluding: a carrier; a plurality of polymer molecules expandable inaqueous solutions, releasably coupled to the carrier; and means forselectively decoupling the polymer molecules from the carrier so thatthe polymer molecules and carrier are released in the stomach.

The decoupling means can include a timer programmable to decouple thepolymer molecules at selected intervals of time, resulting in aprecisely timed, electronically controlled release of the polymermolecules. Moreover, the timer can be activated to decouple the polymermolecules when desired by using, for example, an externalradio-frequency (RF) transmitter. In this embodiment, the decouplingmeans further comprises a miniature RF receiver. The timer and miniatureRF receiver are both operably associated with the carrier. In oneembodiment, the carrier has an internal cavity for housing the timer andRF receiver. In a further embodiment, the decoupling means furthercomprises a battery that may also be housed in the internal cavity ofthe carrier.

The polymer molecules can be selected from a large variety of differentpolymers, and can include a mixture of natural clay and/or various typesof biocompatible polymers, for example, which is not meant to belimiting, superabsorbent and filler material such as Bentonite,microcrystalline hydrogels and polyolefins. Further, if desired, thepolymer molecules can be biodegradable to facilitate the release of thecarrier and polymer molecules from the stomach. The polymer-carryingunit may also further include at least one active agent, which can bereleasably associated with either the carrier or the polymer molecules,or both. The active agent may be selected from a wide group of agents,which include, but are not limited to, enzymatic agents, medicinalagents, chemical agents, or combinations thereof. The polymer moleculesmay be releasably coupled to the carrier by means of electric forces,magnetic forces, electrostatic forces, electromagnetic forces,frictional forces, a fiber, or piezoelectric hinges.

According to another broad aspect of this invention, there is providedan orally administrable polymer-carrying unit for expanding in a stomachof a mammal to fill a space in the stomach, the polymer-carrying unitincluding: a carrier having at least one outer surface; at least onecoupling member having a first surface and a second surface; a pluralityof polymer molecules expandable in the presence of an aqueous solutionassociated with the first surface of the coupling member; a couplingmeans for releasably coupling the second surface of the coupling memberto the outer surface of the carrier; and a decoupling means forselectively decoupling the carrier from the coupling member.

The carrier may adopt a wide variety of different shapes, which caninclude, but are not limited to, sphere-like, triangular-like,pyramid-like, and cube-like shapes. Moreover, the coupling means can beselected from, but are not limited to, an electromagnetic force, africtional force, piezoelectric hinges, or combinations thereof. Thedecoupling means, which may be operably associated with the carrier, canalso be quite diverse, and can comprise a timer, a battery, aradio-frequency receiver, or combinations thereof. In one embodiment,the carrier comprises an internal cavity and the decoupling meanscomprises an electronic device selected from the group consisting of atimer, a battery, a radio-frequency receiver, or combinations thereof,housed within the internal cavity. In one embodiment, the coupling meanscan be a frictional force and the decoupling means can be anelectromagnet operatively associated with the outer surface of thecarrier and means for activating the electromagnet to create a magneticfield. In this embodiment, the coupling member can include a materialthat can be repelled by the magnetic field. In another embodiment, thecoupling means can be a piezoelectric hinge and the decoupling means canproduce an electric voltage to control motion of the piezoelectrichinge.

As mentioned, the polymer molecules can be a mixture of Bentonite and/ora biocompatible polymer, and can be biodegradable. The polymer-carryingunit may also further include at least one active agent, which can bereleasably associated with either the carrier or the polymer molecules,or both. The active agent may be selected from a wide group of agents,which include, but are not limited to, enzymatic agents, medicinalagents, chemical agents, or combinations thereof.

According to another broad aspect of this invention, there is providedan arrangement of polymer-carrying units, the arrangement comprising afirst unit and a second unit, wherein the outer surface of the firstunit is releasably coupled to the outer surface of the second unit bymeans of electric forces, magnetic forces, electrostatic forces,electromagnetic forces, or a combination thereof.

According to another broad aspect of this invention, there is providedan orally administrable dosage form, the dosage form comprising: one ormore polymer-carrying unit or an arrangement of polymer-carrying unitsand at least one pharmaceutically acceptable excipient. The dosage formmay be a capsule, which can be coated with a pH-sensitive coating layer.The pH-sensitive coating layer can be formulated to prevent dissolutionprior to the dosage form reaching the stomach.

According to another broad aspect of this invention, there is providedan orally administrable polymer-carrying unit comprising: a carrierhaving an outer surface and an inner surface, the inner surface formingan internal cavity; at least one fiber for releasably supporting aplurality of sacs, the sacs containing polymer molecules, the fiberbeing threaded into or through the internal cavity of the carrier sothat at least one segment of the fiber is located within the internalcavity; a decoupling means located in the internal cavity for decouplingthe sacs from the carrier by cutting the internal segment of the fiberso that the sacs are released from the carrier. In one embodiment, thedecoupling means comprises an electrical wire located in the internalcavity of the carrier, the electrical wire being heated when desired tomelt and cut the internal segment of the fiber. The polymer moleculescan be a mixture of Bentonite and/or various types of biocompatiblepolymers, for example, which is not meant to be limiting,super-absorbent and filler material such as microcrystalline, hydrogelsand polyolefins. The polymer molecules can also be biodegradable.

According to another broad aspect of this invention, there is provided amethod for the non-invasive reduction of gastric volume, the methodcomprising the steps of: (a) orally administering at least onepolymer-carrying unit as described above; (b) contacting thepolymeric-carrying unit with gastric juice to allow for the polymermolecules to expand and prevent the polymer-carrying unit from exitingthe stomach; and (c) after a desired period of time selectivelydecoupling the polymer molecules from the unit so that exit from thestomach is permitted.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention, both as to its organization and manner ofoperation, may best be understood by reference to the followingdescription, and the accompanying drawings of various embodimentswherein like reference numerals are used throughout the several views,and in which:

FIG. 1A is a schematic view of one embodiment of a polymer-carrying unitaccording to the invention, with the polymer molecules and sacs in anexpanded state.

FIG. 1B is a schematic view of the polymer-carrying unit of FIG. 1A inan encapsulated state.

FIG. 2 is a schematic view of the polymer-carrying unit of FIG. 1A,where the fiber has one cut.

FIG. 3 is a schematic view of the polymer-carrying unit of FIG. 1A,where the fiber has two cuts.

FIG. 4 is a schematic view of another embodiment of a polymer-carryingunit according to the invention having two fibers.

FIG. 5 is a schematic view of the polymer-carrying unit of FIG. 4, whereeach of the fibers have one cut.

FIG. 6 is a schematic view of the polymer-carrying unit of FIG. 4, whereeach of the fibers have two cuts.

FIG. 7 is a schematic view of one embodiment of a decoupling meansaccording to the invention.

FIG. 8 is a schematic view of another embodiment of a polymer-carryingunit according to the invention.

FIG. 9 is a schematic view of another embodiment of a polymer-carryingunit according to the invention.

FIG. 10 is a schematic view of another embodiment of a polymer-carryingunit according to the invention.

FIG. 11 is a schematic view of one embodiment of a decoupling meansaccording to the invention.

FIG. 12 is an exploded view of a portion of the decoupling means of FIG.11.

FIG. 13 is a schematic view of one embodiment of a decoupling meansaccording to the invention.

FIG. 14 is an exploded view of a portion of the decoupling means of FIG.13.

FIG. 15 is a schematic view of one embodiment of a decoupling meansaccording to the invention.

FIG. 16 is an exploded view of a portion of the decoupling means of FIG.15.

FIG. 17 is a schematic view of one embodiment of an arrangement ofpolymer-carrying units according to the invention.

FIG. 18 is a schematic view of one embodiment of an arrangement ofpolymer-carrying units according to the invention.

FIG. 19 is a schematic view of one embodiment of an arrangement ofpolymer-carrying units according to the invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

An orally administrable polymer-carrying unit for expanding in a stomachof a mammal to fill a space in the stomach, as described herein,includes at least a carrier; a plurality of polymer molecules expandablein aqueous solutions that are releasably coupled to the carrier; andmeans for selectively decoupling the polymer molecules from the carrierso that the polymer molecules and carrier are released in the stomach.When the polymer-carrying unit expands in the stomach, the expanded,size of the unit is such that passage of the unit through the pylorus isprevented, which can result in the attainment of a sensation of satietyfor a specified period of time when the stomach remains filled with theunit.

After a desired amount of time has passed, the decoupling means can beactivated in a timed and controlled manner to allow for thedisintegration of the polymer-carrying unit by selectively releasing thepolymer molecules from the carrier. This disintegration can allow thedisintegrated parts of the unit to now pass through the pylorus, andempty from the stomach. The decoupling means can vary widely and caneither be pre-programmed before ingestion or programmed after ingestion.Thus, only certain sections of the polymer-carrying unit can be allowedto disintegrate at one time. This can be particularly useful for thefacilitation of weight loss and the treatment of obesity. Thepolymer-carrying unit can be a non-invasive treatment for obesity thatcan be timed and controlled, which can result in less discomfort to thesubject ingesting the unit.

In the embodiment as illustrated in FIGS. 1-3 and the embodiment asillustrated in FIGS. 4-6, the polymer-carrying unit, referred togenerally as element 10 and 110, respectively, includes a carrier 12having an outer surface 68 and an inner surface 70, with the innersurface forming an internal cavity 72. In this embodiment, polymermolecules 22 are carried in a plurality of sacs 76 that are releasablycoupled to the carrier 12 by at least one fiber 74. The decoupling means26 for selectively decoupling polymer-containing sacs 76 is located ininternal cavity 72 and operates to cut fiber 74 to release the sacs.Desirably, fiber 74 is arranged so as to maximize coverage of carrier 12with sacs 76. If desired, sacs 76 can be supported by fiber 74 throughrings 80, as shown in FIGS. 1-6.

In the embodiment illustrated in FIGS. 1-3, fiber 74 can be threadedthrough internal cavity 72 of the carrier to form a closed loop so thatat least one segment of fiber 74 is located within the internal cavity.Fiber 74 can enter carrier 12 at first location 82 through apertures 84and 86, forming an internal fiber segment 120, and also at secondlocation 88, through apertures 90 and 92, forming internal fiber segment122. Of course, if, desired, more than two locations can also be used.

In the embodiment illustrated in FIGS. 4-6, at least two fibers 74, 75can be connected to carrier 12. As shown in FIG. 13, one fiber 75 can beconnected to carrier 12 at aperture 86 of first location 82, andaperture 92 of second location 88, while the other fiber 74 can beconnected to carrier 12 at aperture 84 of first location 82 and aperture90 of second location 88. In this manner, both fibers 74, 75 can have asegment 124, 126, 128, 130 located within internal cavity 72, which mayfacilitate cutting, as will be discussed below.

In the embodiments illustrated in FIGS. 1-6, polymer molecules 22 caninclude any polymer that can expand when in contact with aqueoussolutions, and can include, but are not limited to, natural clays (forexample, which is not meant to be limiting, Bentonite), microcrystallinehydrogels, polyolefins, polyvinyl alcohol, poly(ethyloxazoline),polyvinylacetate-polyvinylalcohol copolymers,poly(2-hydroxyethylacrylate), poly(2-hydroxyethylmethacrylate),polyacrylic acid, and copolymers thereof, polysaccharides, water solubleproteins, polynucleic acids, or a combination thereof. Polymer molecules22 can be made, if desired, of polyacrylic acid and a crosslinker bysolution or suspension polymerization, using the type and quantity ofcrosslinker to control the swelling capacity and the gel modulus. Thesynthesis and use of such polymer molecules have been previouslydescribed in the following references, incorporated herein by reference:(1) Buchholz and Peppas, Superabsorbent Polymers, ACS Symposium Series,1994; (2) Buchholz and Graham, Modern Superabsorbent Polymer Technology,John Wiley & Sons, 1998; and (3) Biocompatible/Biodegradable Materials(Tutorial). Sigma-Aldrich, 2005, available online at:http://www.sigmaaldrich.com/Area of Interest/Chemistry/MaterialsScience/BiocompatibleBiodegradable/Tutorial.html.

Sacs 76 can be made of an expandable permeable liner. The permeableliner should be able to allow aqueous solutions to enter sacs 76 andcontact polymer molecules 22 to allow for their expansion. In oneembodiment, sacs 76 can be made from natural cellulose fiber orspecialty fiber through spun laced process, spun-bonded polypropylene orabsorbable haemostatic oxidised regenerated cellulose (commerciallyavailable under the name Curasel), and are initially folded, containingthe non-expanded polymer molecules. It may be desirable that thematerial used to construct sacs 76 be expandable, so as to concurrentlyexpand with polymer molecules 22. As a safety feature, sacs 76 may bemade of biodegradable material, so as to allow for biodegradation afterseveral days. Moreover, fiber 74, 75 and rings 80 can also be made of abiocompatible material, which can include, but are not limited to,P-767, Azdel fiber or unreinforced Nylon 612. However, it may bedesirable to select a material for fiber 74, 75 capable of withstandingthe maximum peristaltic force present in the stomach to prevent releaseof sacs 76.

Decoupling means 26, which can be located within internal cavity 72, canbe used to cut an internal segment of fibers 74 and/or 75 to decouple orrelease sacs 76 when exit from the stomach is desirable. As shown inFIGS. 2, 3, 5 and 6, fibers 74 and/or 75 can be cut either at onelocation or at more than one location. Of course, additional cuts canalso be made if desired. One way of cutting can be melting the internalsegment of the fiber. Once fibers 74 and/or 75 is/are cut, sacs 76 canbecome separated from polymer-carrying unit 10.

Decoupling means 26 can take a variety of different forms. In theembodiment illustrated in FIG. 7, decoupling means 26 can include anelectrical wire 100. When appropriate electric current flows throughwire 100, its temperature in the area where it contacts fibers 74 and/or75 increases, and the fiber(s) melts. Fibers 74 and/or 75 is/arepreferably comprised of a material having a low melting point. In oneembodiment, fibers 74 and/or 75 can have a melting point of about 45° C.to about 180° C., for example, P-767, Azdel fiber or unreinforced Nylon612. An electronically-controlled microheater 102 can be used to provideelectrical wire 100 with the required energy to cut fiber 74. In oneembodiment, microheater 102 can generate sufficient energy to raise thetemperature of electrical wire 100 to about 10° C. above the meltingpoint of fiber 74, by allowing an impulse current of appropriatemagnitude to flow through the wire. Wire 100 can be connected to anoutput electronic stage 83, which can be controlled by at least onetimer 85 (as shown in FIG. 7). An RF receiver 87 and battery 89 can alsobe used to control wire 100 in a timed and controlled manner. Thetimer(s), which can be pre-programmed, or can be controlled by the RFreceiver, can be coupled to an electronic output stage designed withstandard power transistors, which can deliver the necessary current tothe electrical wire, so that the microheater increases its temperatureabove the melting point of the fiber, holding the sacs containing theexpanded polymer molecules. For example, which is not meant to belimiting, fiber 74 can be cut at several locations, wherein each cut isperformed over a certain period of time to allow for partialdisintegration, or in embodiments including more than one fiber, i.e.,fibers 74, 75, only one fiber may cut at a certain time. If desired,separate electronic devices may be used for each fiber 74, 75, or foreach cut.

In the embodiment illustrated in FIG. 18, polymer-carrying unit 10 canbe contained within a shell 81, with sacs 76 in a folded conformation tofacilitate oral administration. Shell 81 can be made of a variety ofdifferent materials, which can include, but are not limited to,pH-sensitive materials that will only dissolve under certain conditions,for example, the pH of the stomach. The material used to make the shellcan be the same material, for example, gelatine or cellulose, used tomake pharmaceutical capsules known in the art. Various sizes of shellscan be used, as long as they are swallowable by the patient.

FIGS. 8, 9, and 10 illustrate, in a schematic view, other embodiments ofpolymer-carrying units, 210 a, 210 b and 210 c according to thisinvention, which can be used to facilitate weight loss and to treatobesity, wherein the polymer molecules are releasably coupled to eachunit by different coupling means. Accordingly, each unit will have adecoupling means specific for the particular coupling means.

In general, each polymer-carrying unit 210 a, 210 b, 210 c includes acarrier 212 having an outer surface 214, at least one coupling member216 having a first surface 218 and a second surface 220, a plurality ofpolymer molecules 222 associated with first surface 218 of couplingmember 216, and a coupling means 224 for releasably coupling secondsurface 220 to outer surface 214. Each unit further comprises adecoupling means for selectively decoupling carrier 212 from couplingmember 216, which decoupling means will be discussed in more detailbelow. Decoupling means can allow for polymer-carrying unit 210 a, 210b, 210 c to disintegrate and pass through the pylorus after a certain,controllable period of time.

Carrier 212 can be made of a wide variety of different materials, whichcan include, but are not limited to electrically non-conductive siliconand other biocompatible materials such as composite acrylics. Thecarrier can adopt a wide variety of different shapes. For example, whichis not meant to be limiting, carrier 212 can adopt a sphere-like shape,a triangular-like shape, a pyramid-like shape, or a cube-like shape.Preferably, the carrier comprises internal cavity 272, as shown in FIGS.8-13, which houses the necessary electronics. The electronics can beinsulated and may be further encapsulated within the internal cavity ofthe carrier using electrically non-conductive silicon and otherbiocompatible materials such as composite acrylics.

As discussed above for the embodiments shown in FIGS. 1-6, polymermolecules 22 can include any polymer that can expand when in contactwith aqueous solutions, and can include, but are not limited to, naturalclays (for example, which is not meant to be limiting, Bentonite),microcrystalline hydrogels, polyolefins, polyvinyl alcohol,poly(ethyloxazoline), polyvinylacetate-polyvinylalcohol copolymers,poly(2-hydroxyethylacrylate), poly(2-hydroxyethylmethacrylate),polyacrylic acid, and copolymers thereof, polysaccharides, water solubleproteins, polynucleic acids, or a combination thereof. Moreover, theycan be prepared using a variety of different methods, also discussedabove.

In the embodiments illustrated in FIGS. 8-10, polymer molecules 22 canbe coupled to first surface 218 of coupling member 216 through a varietyof different methods. In one embodiment, polymer molecules having highdensities can be deposited onto the first surface of the coupling memberdirectly. In another embodiment, the polymer molecules may be coupled tothe first surface using glue. The glue may be selected from a widevariety of different glues, which can include, but are not limited to,medical glues such as medical grade cyanoacrylate adhesive. In anotherembodiment (not shown), the polymer molecules may be inserted into a sacmade from a permeable absorbable liner. This liner may be made from avariety of different products, which can include, but are not limitedto, medical gauze and the like. The sac may then be attached to thefirst surface of the coupling member through different ways, including,but not limited to, suturing and/or gluing.

FIGS. 8-13 illustrate that coupling member 216 can be coupled to outersurface 214 in a wide variety of different ways through coupling means224, which can include, but is not limited to, a frictional force (FIGS.8, 9, 11, 13, and 14) and piezoelectric hinges (FIGS. 10, 15, and 16),or combinations thereof. Decoupling means, which can be used to decouplecoupling member 216 from outer surface 214 can include, but is notlimited to, means for producing an electromagnetic force, means forproducing electromagnetically-induced vibrations, means for producingpiezoelectricity, and various electronic devices, which can include, butare not limited to, timers, microcontrollers, power transistors withhigh impulse current delivery capabilities, batteries and/orradio-frequency receivers and transmitters. These devices may be used toprogram the unit to disintegrate after a desired amount of time prior toingestion or after ingestion. For example, which is not meant to belimiting, radio-frequency receivers can receive a signal from atransmitter and allow for the activation of decoupling means afteringestion of polymer-carrying unit 210 a, 210 b, 210 c. Alternatively,again without limiting, the timer(s) can be pre-programmed to initiatethe disintegration of the device after a certain period of time, andwithout the need for external communication with a transmitter.

FIGS. 11 and 12 are illustrative of one embodiment of a decouplingmeans, referred to generally as element numeral 226 a, useful with thepolymeric-carrying unit as illustrated in FIG. 8. In the unit of FIG. 8,coupling means 224 comprises a frictional force that is created by theouter surface 214 of the carrier tightly meshing with coupling member216. In order to prevent separation of coupling member 216 to outersurface 214, the frictional force should desirably be of sufficientstrength to overcome normal peristaltic movement in the stomach. In oneembodiment, the frictional force is set to be at least 2 Newtons. Thisvalue may be calculated assuming that a maximum peristaltic pressure of150 mmHg exerted on a fully expanded polymer on a coupling member 216having dimensions of 1 cm square is about 1.5 Newtons. Of course, thisvalue may be different depending on the dimensions of coupling member216. As shown in FIG. 11, outer surface 214 includes at least twoprojections 228 and 230, which can engage indent 232 of coupling member216 and can create a sufficiently strong mechanical frictional force.

To break the frictional force holding coupling member 216 to outersurface 214, an electromagnet can be used as decoupling means 226 a, asillustrated in FIGS. 11 and 12. As shown in FIGS. 11 and 12, a wire 234is wrapped around the outer surface 214 of carrier 212. Coupling member216 can be made of a biocompatible material with high magneticpermeability, AISI Type 316L Stainless Steel. Outer surface 214 andcoupling member 216 can be repelled from one another by inducing anelectrical current through wire 234 surrounding outer surface 214. Inone embodiment, this electrical current is set to be strong enough sothat the resulting magneto-motive force overcomes coupling means 224(i.e., the frictional forces keeping outer surface 214 and couplingmember 216 together).

As shown in FIG. 12, the electromagnet can include N turns of wire 234carrying a current I around a core of outer surface 214 ofcross-sectional area S and constant permeability μ_(c). The repellingforce exerted on coupling member 216, assuming that the member haspermeability μ_(b) and cross-section S_(b), can be calculated asfollows. It should be noted that the following calculation assumes thata gap is present between coupling member 216 and outer surface 214 (asshown in FIGS. 8, 11 and 12), and that this gap has the samecross-sectional area as outer surface 214 (see FIG. 12).

If it is assumed that coupling member 216 is slightly separated fromouter surface 214 by an air gap of width Z, the magnetic flux φ passingthrough the core and the gap can be obtained as a magnetic voltage droparound the entire magnetic circuit, which subsequently can be related tothe magneto-motive force produced by the electromagnet. φ is expressedas:φ=NI/(Rc+Rb+2Rg)where Rc=Lc/(μ_(c)*S), Rb=Lb/(μ_(b)*Sb) and Rg=z/(μ₀*S) are thereluctances of the core of outer surface 214, coupling member 216 andthe air gap, respectively. The repelling force, Fm, acting on couplingmember 216 can be expressed as:Fm=−(φ²)/(μ₀ *S)

Since the magnetic permeabilities of outer surface 214 and couplingmember 216 are much larger than μ₀, the equivalent reluctance can bemainly dominated by the air gaps reluctance. Lengths Lc and Lb can beset to 1 cm, and S and Sb can be sections of 1 mm×1 cm.

The force required to repel coupling member 216 should be larger thanthe mechanical friction holding the member to outer surface 214 (whichcan be estimated to be 2 Newtons). If such a repelling force is neededfor a 0.25 mm gap between outer surface 214 and coupling member 216, 100windings of the electromagnet would be required for a 1A impulsecurrent.

As discussed above, decoupling means 226 a can be activated after acertain amount of time has passed. FIG. 11 illustrates that decouplingmeans 226 a, including the electromagnet discussed above, can beactivated through a plurality of electronic devices. In this embodiment,carrier 12 has an internal cavity 272 for housing these electronicdevices. These electronic devices can include, but are not limited to, atimer 236, a battery 238, and/or a radio-frequency (RF) receiver 240. Asshown in FIG. 11, timer 236, battery 238 and RF receiver 240 are allelectronically connected. Further, timer 236 can be connected to outersurface 214, which has wire 234 wrapped around it, through wires 242 toallow for controlled repulsion of coupling member 216 from outer surface214. To protect the electronic devices, it may be desirable to covereach device with an insulating material, such as nylon or silicon. Inone embodiment, the insulating material is oxide.

In one embodiment (not shown), separate electronic devices can be usedto control the decoupling of each coupling member from the carrier ofthe polymer-carrying unit. By having a separate electronic timingcontrol, different disintegration patterns can be used. For instance, aseparation to two parts consisting of Y/2 units might occur after 2hours, a separation to 4 smaller parts consisting of Y/4 units mightoccur after 3 hours, etc.

In the polymeric-carrying unit embodiment shown in FIG. 9, couplingmeans 224 includes frictional force. It is understood that thefrictional force must be of sufficient strength to prevent separation ofcoupling member 216 from outer surface 214. In this embodiment, outersurface 214 can further include at least two pegs 244 and 246, which canengage indents 248 and 250, respectively, of coupling member 216 andthus create a sufficiently strong mechanical frictional force.

To break the frictional force holding coupling member 216 to outersurface 214, an electromagnet is used in decoupling means, thedecoupling means referred to generally as element numeral 226 b, asillustrated in FIGS. 13 and 14. As illustrated in FIGS. 13 and 14, anelectromagnet 252 can be embedded within outer surface 214.Electromagnet 252 can be formed by wrapping a wire 254 around aferromagnetic core 256 in multiple windings, while coupling member 216can embed at least one biocompatible permanent magnet 258, for examplebonded Neodymium Iron Boron.

In this embodiment of decoupling means 226 b, outer surface 214 andcoupling member 216 can be repelled from one another by inducingvibrations due to the magnetic interaction between permanent magnet 258embedded in coupling member 216 and electromagnet 252 embedded in outersurface 214. Specifically, an alternating electrical current flowingthrough wire 254 of electromagnet 252 can cause the poles of theelectromagnet to alternate, thus repelling or attracting coupling member216 to outer surface 214 until these vibrations become strong enough sothat the friction force holding them together is overcome. It may bedesirable that this electrical current be sufficiently strong to ensurethat the resulting magneto-motive force can introduce sufficientlystrong vibrations to overcome coupling means 224.

As shown in FIG. 14, electromagnet 252 can consist of N windings ofsingle-loop wire 254 with a winding radius of r, carrying an alternatingcurrent I around a core of cross-sectional area S and constantpermeability μ_(c). Assuming permanent magnet 258 embedded in couplingmember 216 is made from bonded Neodimium Iron Boron of dimensions0.5×0.5 cm, giving a magnetic field Bo=0.7 T, and electromagnet 252embedded in outer surface 214 has similar dimensions with 10 to 20windings, then the magnetic field produced by the electromagnet Bi=μ_(c)NI/2r can also reach the same value, which for convenience will belabeled with B. Consequently, outer surface 214 and coupling member 216can be subjected to dynamic attraction and repulsion changing with thealternating current controlling electromagnet 252. Thus, vibrations canbe introduced with maximum repelling and attracting force of F=I.r.B.

As discussed above for decoupling means 226 a, decoupling means 226 bcan also be controlled through a variety of electronic devices such astimer 236, battery 238 and/or RF receiver 240. Moreover, the electronicdevices can allow selective disintegration of polymer-carrying unit 210,by uncoupling coupling member 216 from outer surface 214 only atcertain, specific locations on the unit.

In the embodiment shown in FIG. 10, coupling means 224 a includespiezoelectric hinges 260, while decoupling means includes electrodeswhich produce an electric voltage. Piezoelectric hinges 260 can be usedto couple coupling member 216 to outer surface 214, and are hingedlyconnected to outer surface 214. The piezoelectric hinges can be made ofa zinc oxide-based biocompatible piezoelectric material, for example oneproduced by Gredmann, San Jose, Calif. In one embodiment, piezoelectrichinges 260 can have dimensions of about 2 to about 3 mm in height, andabout 0.2 to about 0.5 mm in width. In one embodiment, piezoelectrichinges 260 can adopt a general “Γ”-like conformation.

As shown in more detail in FIGS. 15 and 16, coupling member 216 includesa plurality of apertures 264 through which piezoelectric hinges 260 canbe inserted to couple coupling member 216 to outer surface 214. Asdiscussed above, it may be desirable that piezoelectric hinges 260 exerta holding force sufficiently greater than the maximal peristaltic forcein the stomach to prevent decoupling of coupling member 216 and outersurface 214.

To displace piezoelectric hinges from a coupling position, to anuncoupling position in apertures 264, an electric voltage can be appliedthrough electrodes 262 of the decoupling device shown in FIG. 16,referred to generally as element numeral 226 c. In one embodiment, byapplying electric voltage to piezoelectric hinges 260, a displacementranging between 10 to 20% from the coupling position to the uncouplingposition can be produced, which can allow for the piezoelectric hingesto detach from coupling member 216 and exit through apertures 264 incoupling member 216. In the uncoupling position, piezoelectric hinges260 can no longer engage and retain coupling member 216, which can bereleased from outer surface 214.

Decoupling means 226 c useful in the embodiment illustrated in FIG. 10,can be controlled through a variety of electronic devices such as timer236, battery 238 and/or RF receiver 240, as shown in FIGS. 10 and 15.Moreover, the electronic devices can allow selective disintegration ofpolymer-carrying unit 210, by uncoupling coupling member 216 from outersurface 214 only at certain, specific locations on the unit.

FIGS. 17-19 illustrate further embodiments according to the invention.In these embodiments, a plurality of polymer-carrying units can beinterconnected to form an arrangement. In the embodiment illustrated inFIG. 17, one of the outer surfaces 314 of polymer-carrying unit 310 a isextended by means of a spacer 317 and has a wire 334 operably attachedat its extremity. Another polymer-carrying unit 310 b also has anextended outer surface 314, which is extended by means of spacer 317 andis adapted to frictionally receive the extended outer surface ofpolymer-carrying unit 310 a as described above. Decoupling means can beused to decouple the polymer-carrying units as described above.Moreover, as discussed above, decoupling means dedicated only to thedecoupling of one unit from another may be used to allow for partialdisintegration of the arrangement.

In the embodiment shown in FIG. 18, outer surface 314 ofpolymer-carrying unit 310 c is extended by means of a spacer 317. Outersurface 314 can include electromagnet 352 embedded at its extremity.Outer surface 314 of polymer-carrying unit 310 d is also extended bymeans of spacer 317 and the outer surface extremity includes abiocompatible permanent magnet 358 embedded therein. Outer surface 314of polymer-carrying unit 310 c further includes pegs 344 and 346, whichare frictionally received by the outer surface of polymer-carrying unit310 d, as described above. Decoupling means can be used to decouple thepolymer-carrying units, as described above. Moreover, as discussedabove, decoupling means dedicated only to the decoupling of one unitfrom another may be used to allow for partial disintegration of thearrangement.

In the embodiment illustrated in FIG. 19, one of the outer surfaces 314of polymer unit 310 f can be extended by means of a spacer 317, and caninclude piezoelectric hinges 360. One of the outer surface 314 ofpolymer-carrying unit 310 e can also be extended by a spacer 317 and caninclude apertures 364 for receiving the hinges, as described above.Decoupling means can be used to decouple the units as described above.Moreover, as described above, decoupling means dedicated only to thedecoupling of one unit from another may be used to allow for partialdisintegration of the arrangement.

It may be desirable to include spacers 317 within polymer-carrying unit10 in order to allow for the addition of various active agents. Activeagents may be selected from the group consisting of enzymatic agents,medicinal agents, chemical agents, or combinations thereof. For example,which is not meant to be limiting, it may be desirable to delivervarious pharmaceutical agents that also facilitate weight loss, orenzymes that may accelerate degradation of polymer molecules 322.However, the active agents can also be added to sacs 376, or associatedwith polymer molecules 322.

According to another embodiment of this invention, there is provided anorally-administrable pharmaceutical dosage form including at least onepolymer-carrying unit and, if desired, a pharmaceutically acceptableexcipient such as binders, fillers and disintegrants, for example,starch. The pharmaceutical dosage form may take various forms, whichinclude, but are not limited to, liquids, soft substances, powder-likesubstances, and hard pharmaceutical substances such as soft capsules,hard capsules and tablets. In one embodiment, the pharmaceutical dosageform is a capsule. In another embodiment, the capsule can be coated witha pH-sensitive coating. The pH-sensitive coating may prevent dissolutionuntil the stomach reached, to prevent contact between polymer molecules22 and aqueous solutions.

The administration of a polymer-carrying unit or a dosage form includingat least one polymer-carrying unit can be used as a non-invasivetechnique for the reduction of gastric volume. The unit or a dosage formincluding at least one unit can be administered by mouth, where it willreach the stomach. Once in the stomach, the polymer molecules can becontacted with aqueous solutions, which will result in their expansion.The expanded polymer molecules, which cannot pass through the pylorus,can fill a significant portion of the volume of the stomach, resultingin the attainment of a feeling of satiety. After a desired period oftime has passed, polymer molecules can be selectively decoupled from theunit, or portions of the dosage form can be selectively decoupled fromone another, in order for the decoupled portions to exit the stomachthrough normal peristaltic movement.

While the invention has been described in conjunction with the disclosedembodiments, it will be understood that the invention is not intended tobe limited to these embodiments. On the contrary, the current protectionis intended to cover alternatives, modifications and equivalents, whichmay be included within the spirit and scope of the invention. Variousmodifications will remain readily apparent to those skilled in the art.

What is claimed is:
 1. An orally administrate polymer-carrying unit for expanding in a stomach of a mammal to fill a space in the stomach and deliver at least one active agent thereto, the polymer-carrying unit comprising: (a) a carrier having an outer surface, an inner surface, and an internal cavity formed by the inner surface; (b) at least one coupling member disposed externally of the carrier and having a first surface facing away from the carrier and a second surface facing toward the carrier; (c) a plurality of polymer molecules, expandable in the presence of an aqueous solution, coupled to the first surface of the coupling member; (d) a coupler releasably coupling the second surface of the coupling member to the outer surface of the carrier; and (e) a decoupler comprising an electronic device housed within the internal cavity of the carrier and arranged for selectively decoupling the coupling member from the carrier; and (f) an active agent releasably associated with the carrier, the coupling member, the polymer molecules, or a combination thereof.
 2. The polymer-carrying unit as claimed in claim 1, the carrier having a sphere-like shape.
 3. The polymer-carrying unit as claimed in claim 1, the carrier having a triangular-like or pyramid-like internal shape.
 4. The polymer-carrying unit as claimed in claim 1, the carrier having a cube-like shape.
 5. The polymer-carrying unit as claimed in claim 1, wherein the coupler is selected from the group consisting of means for producing an electromagnetic force, means for producing a frictional force, piezoelectric hinges, or combinations thereof.
 6. The polymer-carrying unit as claimed in claim 1, wherein the electronic device of the decoupler is selected from the group consisting of a timer, a battery, a radio-frequency receiver, or combinations thereof.
 7. The polymer-carrying unit as claimed in claim 1, wherein the coupler comprises means for producing a frictional force and the decoupler comprises an electromagnet operatively associated with the outer surface of the carrier and means for activating the electromagnet to create a magnetic field.
 8. The polymer-carrying unit as claimed in claim 7, wherein the coupling member comprises a material that can be repelled by the magnetic field.
 9. The polymer-carrying unit as claimed in claim 1, wherein the coupler is at least one piezoelectric hinge and the decoupler is arranged to produce an electric voltage.
 10. The polymer-carrying unit as claimed in claim 1, wherein the polymer molecules are a mixture of natural clay and a biocompatible polymer.
 11. The polymer-carrying unit as claimed in claim 1, wherein the polymer molecules are biodegradable.
 12. The polymer-carrying unit as claimed in claim 1, wherein the active agent is selected from the group consisting of enzymatic agents, medicinal agent, chemical agents, or combinations thereof.
 13. An arrangement of polymer-carrying units as claimed in claim 1, the arrangement comprising a first unit and a second unit, wherein the outer surface of the first unit is releasably coupled to the outer surface of the second unit by means of electric forces, magnetic forces, electrostatic forces, electromagnetic forces, or a combination thereof.
 14. A orally administrable dosage form, the dosage form comprising: (a) one or more polymer-carrying units each comprising: (i) a carrier having an outer surface, an inner surface, and an internal cavity formed by the inner surface; (ii) at least one coupling member disposed externally of the carrier and having a first surface facing away from the carrier and a second surface facing toward the carrier; (iii) a plurality of polymer molecules, expandable in the presence of an aqueous solution, coupled to the first surface of the coupling member; (iv) a coupler releasably coupling the second surface of the coupling member to the outer surface of the carrier; and (v) a decoupler comprising an electronic device housed within the internal cavity of the carrier and arranged for selectively decoupling the coupling member from the carrier; and (b) at least one pharmaceutically acceptable excipient.
 15. The orally administrable dosage form of claim 14, wherein the dosage form is a capsule.
 16. The orally administrable dosage form of claim 15, wherein the capsule is coated with a pH-sensitive coating layer.
 17. The orally administrable dosage form of claim 13, wherein the coating layer is arranged to dissolve in gastric juice. 